Intraperitoneal drug administration pharmacokinetics

A pro-drug approach for improving the pharmacokinetics of zanamivir has recently shown some promise. The alkoxyalkyl ester 23 of zanamivir, with long alkyl chains chosen to counteract the high hydrophUicity of the molecule, was reported to show significant protective effects against influenza (HlNl) infection in mice upon oral or intraperitoneal administration (Liu et al. 2007). 

Some pharmacokinetic properties of the commonly used amide local anesthetics are summarized in Table 26-2. The pharmacokinetics of the ester-based local anesthetics have not been extensively studied owing to their rapid breakdown in plasma (elimination half-life < 1 minute). Local anesthetics are usually administered by injection into dermis and soft tissues around nerves. Thus, absorption and distribution are not as important in controlling the onset of effect as in determining the rate of offset of local analgesia and the likelihood of CNS and cardiac toxicity. Topical application of local anesthetics (eg, transmucosal or transdermal) requires drug diffusion for both onset and offset of anesthetic effect. However, intracavitary (eg, intra-articular, intraperitoneal) administration is associated with a more rapid onset and shorter duration of local anesthetic effect. 

Substantial progress has also been reported with regard to the synthesis and testing of nuclease-resistant ribozyme drugs. Modifications including phosphorothioates and nucleoside analogs have been demonstrated to be incorporable in many sites in hammerhead ribozymes, to increase nuclease resistance and support retained ribozyme activity (59-61). In fact, modified relatively nuclease-resistant ribozymes were reported to decrease the target, stromelysin, mRNA levels in knee joints of rabbits after intra-articular injection (62). Further, the pharmacokinetics of a relatively nuclease-stable hammerhead ribozyme were determined after intravenous (i.v.), subcutaneous (s.c.), or intraperitoneal (i.p.) administration to mice. The ribozyme... 

Fujita T, Tamura T, Yamada H, Yamamoto A, Muranishi S. Pharmacokinetics of mitomycin C (MMC) after intraperitoneal administration of MMC-gelatin gel and its anti-tumor effects against sarcoma-180 bearing mice. J Drug Target 1997 4 289-296. 

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